鼠乳腺瘤病毒（MMTV）与人乳腺癌——布拉德福·希尔标准的价值。
Mouse Mammary Tumour Virus (MMTV) in Human Breast Cancer-The Value of Bradford Hill Criteria.
机构信息
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney 2052, Australia.
出版信息
Viruses. 2022 Mar 30;14(4):721. doi: 10.3390/v14040721.
UNLABELLED
For many decades, the betaretrovirus, mouse mammary tumour virus (MMTV), has been a causal suspect for human breast cancer. In recent years, substantial new evidence has been developed. Based on this evidence, we hypothesise that MMTV has a causal role. We have used an extended version of the classic A. Bradford Hill causal criteria to assess the evidence. 1. Identification of MMTV in human breast cancers: The MMTV 9.9 kb genome in breast cancer cells has been identified. The MMTV genome in human breast cancer is up to 98% identical to MMTV in mice. 2.
EPIDEMIOLOGY
The prevalence of MMTV positive human breast cancer is about 35 to 40% of breast cancers in Western countries and 15 to 20% in China and Japan. 3. Strength of the association between MMTV and human breast cancer: Consistency-MMTV env gene sequences are consistently five-fold higher in human breast cancer as compared to benign and normal breast controls. 4. Temporality (timing) of the association: MMTV has been identified in benign and normal breast tissues up to 10 years before the development of MMTV positive breast cancer in the same patient. 5.
EXPOSURE
Exposure of humans to MMTV leads to development of MMTV positive human breast cancer. 6. Experimental evidence: MMTVs can infect human breast cells in culture; MMTV proteins are capable of malignantly transforming normal human breast epithelial cells; MMTV is a likely cause of biliary cirrhosis, which suggests a link between MMTV and the disease in humans. 7. Coherence-analogy: The life cycle and biology of MMTV in humans is almost the same as in experimental and feral mice. 8. MMTV Transmission: MMTV has been identified in human sputum and human milk. Cereals contaminated with mouse fecal material may transmit MMTV. These are potential means of transmission. 9. Biological plausibility: Retroviruses are the established cause of human cancers. Human T cell leukaemia virus type I (HTLV-1) causes adult T cell leukaemia, and human immunodeficiency virus infection (HIV) is associated with lymphoma and Kaposi sarcoma. 10. Oncogenic mechanisms: MMTV oncogenesis in humans probably differs from mice and may involve the enzyme APOBEC3B.
CONCLUSION
In our view, the evidence is compelling that MMTV has a probable causal role in a subset of approximately 40% of human breast cancers.
未加标签
几十年来，β逆转录病毒——鼠乳腺肿瘤病毒（MMTV）一直是人类乳腺癌的致病嫌疑物。近年来，大量新的证据已经出现。基于这些证据，我们假设 MMTV 具有因果关系。我们使用了经典 A. Bradford Hill 因果关系标准的扩展版本来评估证据。1. MMTV 在人类乳腺癌中的鉴定：乳腺癌细胞中的 MMTV 9.9kb 基因组已被鉴定。人类乳腺癌中的 MMTV 基因组与小鼠中的 MMTV 高达 98%相同。2. 流行病学：在西方国家，MMTV 阳性的人类乳腺癌的患病率约为 35%至 40%，在中国和日本则为 15%至 20%。3. MMTV 与人类乳腺癌之间关联的强度：一致性——与良性和正常乳腺对照相比，人类乳腺癌中的 MMTV env 基因序列始终高出五倍。4. 关联性的时间性（时间）：在同一患者中，MMTV 已在良性和正常乳腺组织中鉴定出，其时间早于 MMTV 阳性乳腺癌的发展达 10 年。5. 暴露：人类接触 MMTV 会导致 MMTV 阳性的人类乳腺癌的发展。6. 实验证据：MMTV 可以感染人类乳腺细胞培养物；MMTV 蛋白能够恶性转化正常人类乳腺上皮细胞；MMTV 是胆汁性肝硬化的一个可能原因，这表明 MMTV 与人类疾病之间存在联系。7. 一致性-类比：人类 MMTV 的生命周期和生物学几乎与实验和野生小鼠相同。8. MMTV 传播：MMTV 已在人类痰液和人乳中鉴定出。受鼠粪便污染的谷物可能会传播 MMTV。这些是潜在的传播途径。9. 生物学合理性：逆转录病毒是人类癌症的既定原因。人类 T 细胞白血病病毒 I 型（HTLV-1）导致成人 T 细胞白血病，人类免疫缺陷病毒感染（HIV）与淋巴瘤和卡波西肉瘤有关。10. 致癌机制：人类 MMTV 致癌可能与小鼠不同，可能涉及酶 APOBEC3B。
结论
在我们看来，证据令人信服地表明，MMTV 在大约 40%的人类乳腺癌中具有可能的因果作用。
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